EPA scientists work to advance the science of chemical risk assessment.

Everyday activities – actions as simple as biting into an apple, or walking across a carpeted floor – may expose people to a host of chemicals through a variety of pathways. The air we breathe, the food and water we consume, and the surfaces we touch all are the homes of natural and synthetic chemicals, which enter our bodies through our skin, our digestive systems, and our lungs.

This makes determining how (and how much of) certain chemicals enter our bodies challenging. In most cases, there is not one single source for any given chemical that may be found in our bodies. Using sophisticated computer models and methods, EPA scientists have developed an innovative set of tools to estimate total exposures and risks from chemicals encountered in our daily lives.

“The traditional approach of assessing the risk from a single chemical and a single route of exposure (such as breathing air) may not provide a realistic description of real-life human exposures and the cumulative risks that result from those exposures,” said EPA scientist Dr. Valerie Zartarian. “Risk assessments within EPA are now evolving toward the ‘cumulative assessments’ mandated by the Food Quality Protection Act and the Safe Drinking Water Act.”

Moving the science of chemical risk assessments forward to where it’s possible to evaluate total risks from exposures to a wide variety of chemicals requires several key pieces of information. You need to know what chemicals are found in the environment, their concentration levels in the environment, and how they come into contact with humans. You also have to know how they enter the body, and what they do after that.

EPA’s Stochastic Human Exposure and Dose Simulation (SHEDS) model addresses the first part of this problem. SHEDS can estimate the range of total chemical exposures in a population from different exposure pathways (inhalation, skin contact, dietary and non-dietary ingestion) over different time periods, given a set of demographic characteristics. The estimates are calculated using available data, such as dietary consumption surveys; human activity data drawn from EPA's Consolidated Human Activities Database (CHAD); and observed chemical levels in food, water, air, and on surfaces like floors and counters.

The data on chemical concentrations and exposure factors used as inputs for SHEDS are based on measurements collected in EPA field studies and published literature values. "EPA’s observational exposure studies have also provided information and data to help define the processes simulated in the model, and evaluate or "ground-truth" SHEDS model estimates", said Zartarian, "who co-developed the model with Dr. Jianping Xue, Dr. Haluk Ozkaynak, and others."

“The concept of SHEDS is to first simulate an individual over time,” she explained. “The model calculates that individual’s sequential exposures to concentrations in different media and across multiple pathways, and then applies statistical methods to give us an idea of how these exposures might look across a whole population.”

The story of how chemicals enter the human body doesn’t end there, however. The exposure estimates that SHEDS generates are now being used as inputs for another kind of model – a physiologically based pharmacokinetic (or PBPK) model, which predicts how chemicals move through and concentrate in human tissues and body fluids.

Using PBPK models, scientists can take the estimates of chemical exposures across multiple pathways generated by SHEDS and examine how these will impact organs and tissues in the body, and determine how long they will eventually take to be naturally processed and expressed.

Together, these two models provide scientists with a much more accurate picture of the risk certain chemicals pose to human health – a picture they’ve been able to confirm by extensive comparisons against real-world data, such as duplicate diet and biometric data collected by the U.S. Centers for Disease Control and Prevention in the National Health and Nutrition Examination Survey (NHANES), which collects biomarker data from 5,000 people each year. When EPA researchers have compared the SHEDS-PBPK exposure and dose estimates with the physical NHANES data, they’ve found that the model’s predictions line up very closely with the observations in the survey.

“The real-world grounding gives you a lot of confidence in the exposure routes modeled in SHEDS and PBPK,” said Rogelio Tornero-Velez, an EPA scientist who has helped develop the Agency’s PBPK models used in the study.

SHEDS has already been used in developing EPA’s regulatory guidance on organophosphate and carbamate pesticides, and chromated copper arsenate, a chemical wood preservative once used on children’s playground equipment. Now, EPA researchers are using the coupled SHEDS-PBPK models to examine a relatively new class of chemical pesticides called pyrethroids to determine whether they pose any risk to human health and the environment.

EPA scientists are continuing to refine the SHEDS and PBPK models used in these studies, adding functions and testing them against real-world data. For policy makers, these models will serve as invaluable tools in making decisions meant to protect human health and the environment from the risk of exposure to harmful chemicals.

“The science and software behind SHEDS and PBPK are substantial,” said David Miller, who has worked on the project from EPA’s regulatory perspective. “They provide exposure and risk assessors both within and outside EPA with a physically-based, probabilistic human exposure model for multimedia, multi-pathway chemicals that is in many ways far superior to those that are presently in routine use.”